1. Field of the Invention
The present invention relates to a pharmaceutical composition containing a quinolinone derivative, which is useful as an anti-allergy agent, and to a production method therefor.
2. Description of Related Art
A quinolinone derivative represented by the structural formula (I):
is a compound disclosed in Japanese Unexamined Patent Application, First Publication No. Hei 9-255659 (corresponding U.S. Pat. No. 5,942,521) and is useful as an anti-allergy agent which has low toxicity in the living body and is particularly effective against immediate allergy diseases and delayed allergy diseases such as immediate type asthma, delayed type asthma, bronchial asthma, pediatric asthma, hypersensitivity pneumonitis, atopic dermatitis, allergic dermatitis, urticaria, eczema, allergic conjunctivitis, allergic rhinitis, hay fever, food allergy, allergic gastroenteritis, allergic colitis, contact dermatitis, and autoimmune diseases.
However, since the quinolinone derivative is a slightly soluble drug, the dissolution rate of a pharmaceutical preparation produced by the method described in the publication described above in the digestive tract is not always satisfactory and an absorption ratio and an absorption rate are likely to change. Therefore, it has been required to develop a pharmaceutical composition wherein the dissolution rate of the quinolinone derivative in the digestive tract is improved, thereby improving the absorbability.
On the other hand, Japanese Unexamined Patent Application, First Publication No. Hei 11-255649 describes that the quinolinone derivative is polymorphism in its crystal form and includes four kinds of crystal forms such as α-type crystal, β-type crystal, γ-type crystal and δ-type crystal and, particularly, β-type crystal and γ-type crystal are superior in bioabsorbability to the α-type crystal. The same publication describes that particles obtained by grinding the quinolinone derivatives in the respective crystal forms for about 10 minutes using an automatic agate mortar have improved bioabsorbability as compared with the bioabsorbability before grinding. However, when the quinolinone derivative is ground by such a method, there arose a problem that the crystallinity of the quinolinone derivative is lowered and, as a result, the physicochemical stability of the resulting quinolinone derivative is lowered.